Fish Oil in pREgnancY for Personalized Prevention of Early Childhood Asthma (FREYA)

Fish Oil in pREgnancY for Personalized Prevention of Early Childhood Asthma (FREYA)

The overall aim of the study is to develop a nutritional preventive fish oil supplementation strategy in pregnancy for early childhood asthma/persistent wheeze during the first three years of life as we hypothesize that both supplementations in higher doses than recommended could reduce the risk of disease development.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Tract Infections; Fractures, Bone; Asthma; Allergy; Eczema; Croup; Development, Child; Gastrointestinal Infection; Wheezing; Psychiatric Diagnosis; Cognition Disorders in Children
• Intervention / Treatment: Dietary supplement: n-3 fatty acid; Other: Rape seed oil

Detailed Description

Randomization of 2000 pregnant women to fish oil of 2.4 g/day (55% EPA and 37% DHA) in triacylglycerol form vs placebo. Supplementation begins in gestational week 24 (22-26) until 1 week after delivery. Allocation to the trial will be determined based on the pre-interventional maternal blood levels of EPA+DHA with a dried blood screening test. Women with low levels (below 4.7% of total fatty acids) will be assigned to the fish oil RCT. Maternal blood will be used for genetic, metabolomic and proteomic profiling. A 3-year follow-up of the children with longitudinal registration of parent reported symptoms, diagnoses, medication use, and hospitalizations will be performed. The primary outcome is persistent wheeze or asthma until age 3 years, with predefined analyses of effect modification by maternal genotypes. Secondary outcomes are lower respiratory tract infections, gastrointestinal infections, croup, troublesome lung symptoms, eczema, allergy, bone fractures, developmental milestones, mental health, cognition, and growth until age 3 years. A follow-up on both primary and secondary outcomes is planned after unblinding, from age 3 to 6 years.

• Study Type: Interventional
• Enrollment (Estimated): 2000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Klaus Bønnelykke, PhD; Phone Number: +45 38677360; Email: kb@copsac.com
• Study Contact Backup: Name: Ulrik Ralfkiaer, PhD; Phone Number: +45 38674164; Email: administration@dbac.dk

Study Locations

• Denmark
  • Gentofte Municipality, Denmark, DK-2820
    • Recruiting
    • Copenhagen University Hospital of Copenhagen
    • Contact: Klaus Bønnelykke, PhD; Phone Number: +45 38677360; Email: kb@copsac.com
    • Contact: Ulrik Ralfkiaer, PhD; Phone Number: +45 38674164; Email: ulrik.ralfkiaer@dbac.dk
    • Principal Investigator: Klaus Bønnelykke, PhD
    • Principal Investigator: Bo Chawes, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

• Pregnant Danish women before week 26 with blood levels of EPA+DHA below 4.7% of total fatty acids
• No planned use of fish oil supplementations
• No endocrine-, heart-, kidney- or auto-immune disorders
• No disorders requiring treatment with blood thinning medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: n-3 fatty acid of 2.4 g per day; Oral intake of 4 capsules daily from week 22-26 of gestation until 1 week after delivery	Dietary supplement: n-3 fatty acid; Oral intake of 4 capsules per day from week 22-26 in pregnancy to 1 week after delivery; Other Names: GoldenOmega, PharmaNord, DK
Placebo Comparator: Rape seed oil; Oral intake of 4 capsules daily from week 22-26 of gestation until 1 week after delivery	Other: Rape seed oil; Oral intake of 4 capsules per day from week 22-26 in pregnancy to 1 week after delivery; Other Names: Placebo capsules, PharmaNord, DK

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early childhood asthma/persistent wheeze age 0-3 years	Defined as either a) parental report of a minimum of 2 wheeze episodes with at least 1 after the child's second birthday and redemption of at least 2 prescriptions of asthma controller medication with at least 1 being after the child's second birthday or b) a minimum of 2 ED visits or hospitalizations due to asthmatic symptoms, and at least 1 of these being after the child's second birthday or c) parental report of physician-diagnosed asthma age 0-3 years Outcome analysis: risk (survival analysis) of persistent wheeze or asthma at age 0-3 years.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atopic/non-atopic wheeze or asthma age 0-3 years	Parental reports of physician diagnosed asthma in combination with eczema and/or allergic rhinitis. Outcome analyses: asthma/persistent wheeze with/without eczema and/or allergic rhinitis (yes/no) by age 3 years. Each subtype is compared with children without asthma.	3 years
Troublesome lung symptoms age 0-3 years	Defined as cough, wheeze or dyspnea severely affecting the well-being of the child for at least 3 consecutive days based on parental reports. Outcome analyses: total no. of episodes with symptoms age 0-3 years.	3 years
Wheeze episodes age 0-3 years	Parental reports of wheezing. Outcome analyses: total no. of episodes with wheeze age 0-3 years.	3 years
Inhaled bronchodilator use from parental reports age 0-3 years	Outcome analyses: total no. of days with bronchodilator use age 0-3.	3 years
Inhaled bronchodilator prescriptions from medical record checks age 0-3 years	Outcome analyses: total no. of prescriptions age 0-3.	3 years
Asthma controller medication use from parental reports age 0-3 years	Outcome analyses: total no. of days with use of asthma controller medication age 0-3.	3 years
Asthma controller medication prescriptions from medical record checks age 0-3 years	Outcome analyses: total no. of prescriptions age 0-3.	3 years
Asthma hospitalizations or emergency department visits age 0-3 years	Outcome analyses: total no. of episodes age 0-3 years.	3 years
Eczema age 0-3 years	Parental reports of physician-diagnosed eczema and prescribed topical antiinflammatory medication on medical record checks. Outcome analyses: risk (survival analysis) of any eczema age 0-3 years and current eczema (yes/no) by age 3 years.	3 years
Allergic rhinitis age 0-3 years	Based on parental reports of physician-diagnosed allergic rhinitis. Outcome analyses: allergic rhinitis (yes/no) by age 3 years.	3 years
Food allergy 0-3 years	Parental reports of physician-diagnosed food allergy. Outcome analyses: any food allergy (yes/no) by age 3 years.	3 years
Lower respiratory tract infections age 0-3 years	Parental reports of physician-diagnosed bronchiolitis or pneumonia. Outcome analysis: risk (survival analysis) of first lower respiratory tract infection and total no. of lower respiratory tract infections age 0-3 years.	3 years
Gastrointestinal infections age 0-3 years	Parental reports. Outcome analyses: risk (survival analysis) of any gastroenteritis episode and total no. of gastroenteritis episodes age 0-3 years.	3 years
Croup age 0-3 years	Parental reports of physician diagnosed croup. Outcome analysis: risk (survival analysis) of any croup episode and total no. of croup episodes age 0-3 years.	3 years
Fever episodes age 0-3 years	Based on parental reports. Outcome analyses: total no. of episodes with symptoms age 0-3 years.	3 years
Absences from daycare age 0-3 years	Due to illnesses based on parental reports. Outcome analyses: total no. of absence days age 0-3 years.	3 years
Bone fractures age 0-3 years	Assessed by medical record checks including all radiologically verified fractures of larger long bones (i.e. clavicle, radius, ulna, tibia, fibula, femur and humerus). Outcome analyses: total no. of fractures age 0-3 years.	3 years
Developmental milestones age 0-3 years	Monitored every 6 months until age 3 years by the parents using a registration form based on The Denver Development Index and WHO milestones registration. Outcome analyses: combined assessment of age at achievement across milestones by principal component analysis.	3 years
Strength and difficulties at age 3 years	From the Strengths and Difficulties Questionnaire (SDQ), which is a brief behavioral screening questionnaire. Outcome analyses: SDQ scores at age 3 years.	3 years
ADHD symptoms at age 3 years	From the ADHD rating scale-IV preschool, a dimensional questionnaire for ADHD symptoms in preschool children. Outcome analyses: ADHD symptom scores at age 3 years.	3 years
Social behavior assessment at age 3 years	From the Social Responsiveness Scale, Second Edition; a questionnaire for screening for autistic traits: Outcome analyses: Total problem scores at age 3 years.	3 years
Psychopathology screening at age 3 years	From the Child Behavior Check List 1,5-5 years; a questionnaire for general screening of preschool psychopathology. Outcome analyses: Total syndrome scales at age 3 years.	3 years
Cognitive assessment age 0-3 years	From Behavior Rating Inventory of Executive Function in preschool children; a measurement of executive functions. Outcome analyses: Index values at age 3 years.	3 years
BMI and waist circumference age 0-3 years	From parental reports every 6 months. Outcome analyses: development of BMI and waist circumference age 0-3 years and current BMI and waist circumference at age 3.	3 years
Persistent wheeze or asthma age 0-6 years	Defined similarly to the primary outcome Outcome analysis: risk (survival analysis) of persistent wheeze or asthma at age 0-6 years	6 years
Current asthma at age 6 years	Defined similarly to the primary outcome and with symptoms and/or asthma medication use in the last 12 months at age 6. Outcome analyses: Current wheeze or asthma (yes/no) by age 6 years.	6 years
Asthma or wheeze yearly prevalence 0-6 years	Defined as in the primary outcome and current disease defined from parental reports of wheeze and/or asthma medication use. Outcome analyses: Yearly prevalence of wheeze or asthma medication use (yes/no) 0-6 years.	6 years
Atopic/non-atopic asthma at age 6 years	Parental reports of physician diagnosed asthma in combination with eczema and/or allergic rhinitis. Outcome analyses: Current asthma with/without eczema and/or allergic rhinitis (yes/no) by age 6 years. Each subtype is compared with children without asthma.	6 years
Asthma controller medication 0-6 years	From redeemed medication prescriptions (inhaled corticosteroids and leukotriene modifiers) based on medical record checks: Outcome analyses: total no. of prescriptions age 0-6 years.	6 years
Inhaled bronchodilators age 0-6 years	From redeemed inhaled bronchodilators based on medical record checks. Outcome analyses: total no. of prescriptions age 0-6 years.	6 years
Asthma hospitalizations or emergency department visits age 0-6 years	Based on medical record checks. Outcome analyses: total no. of episodes age 0-6 years.	6 years
Eczema age 0-6 years	Based on parental reports of physician diagnosed eczema. Outcome analyses: risk (survival analysis) of any eczema age 0-6 years and current eczema (yes/no) by age 6 years.	6 years
Allergic rhinitis age 0-6 years	Based on parental reports of physician-diagnosed allergic rhinitis and on medical record checks. Outcome analyses: allergic rhinitis (yes/no) by age 6 years.	6 years
Food allergy age 0-6 years	Based on parental reports of physician-diagnosed food allergy. Outcome analyses: any food allergy (yes/no) by age 6 years.	6 years
Lower respiratory tract infections age 0-6 years	Based on parental reports of physician-diagnosed bronchiolitis or pneumonia. Outcome analysis: risk (survival analysis) of first lower respiratory tract infection and total no. of lower respiratory tract infections age 0-6 years.	6 years
Gastrointestinal infections age 0-6 years	Based on parental reports. Outcome analyses: risk (survival analysis) of any gastroenteritis episode and total no. of gastroenteritis episodes age 0-6 years.	6 years
Croup age 0-6 years	Based on parental reports of physician diagnosed croup. Outcome analysis: risk (survival analysis) of any croup episode and total no. of croup episodes age 0-6 years.	6 years
Bone fractures age 0-6 years	Assessed by medical record checks including all radiologically verified fractures of larger long bones (i.e. clavicle, radius, ulna, tibia, fibula, femur and humerus). Outcome analyses: total no. of fractures age 0-6 years.	6 years
Strength and difficulties at age 6 years	From the Strengths and Difficulties Questionnaire (SDQ), which is a brief behavioral screening questionnaire. Outcome analyses: SDQ scores at age 6 years.	6 years
ADHD symptoms at age 6 years	From the ADHD rating scale-IV preschool, a dimensional questionnaire for ADHD symptoms in preschool children. Outcome analyses: ADHD symptom scores at age 6 years.	6 years
Social behavior assessment at age 6 years	From the Social Responsiveness Scale, Second Edition; a questionnaire for screening for autistic traits. Outcome analyses: Total problem scores at age 6 years.	6 years
Psychopathology screening at age 6 years	From the Child Behavior Check List; a questionnaire for general screening of preschool psychopathology. Outcome analyses: Total syndrome scales at age 6 years.	6 years
Cognitive assessment age 0-6 years	From Behavior Rating Inventory of Executive Function in preschool children; a measurement of executive functions. Outcome analyses: Index values at age 6 years.	6 years
BMI and waist circumference age 0-6 years	From parental reports every 6 months. Outcome analyses: development of BMI and waist circumference age 0-6 years and current BMI and waist circumference at age 6.	6 years

Collaborators and Investigators

• Sponsor: Professor Klaus Bønnelykke
• Investigators: Principal Investigator: Bo Chawes, PhD, Copenhagen Studies on Asthma in Childhood; Principal Investigator: Klaus Bønnelykke, PhD, Copenhagen Studies on Asthma in Childhood

Publications and helpful links

General Publications

• Brustad N, Vahman N, Ralfkiaer U, Mikkelsen M, Brandt S, Kyvsgaard JN, Vinding R, Stokholm J, Chawes B, Bonnelykke K. Fish oil and vitamin D in pregnancy for the prevention of early childhood asthma: study protocol for two double-blinded, randomised controlled trials. BMJ Open. 2024 Dec 31;14(12):e092902. doi: 10.1136/bmjopen-2024-092902.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): March 1, 2033

Study Registration Dates

• First Submitted: August 15, 2024
• First Submitted That Met QC Criteria: August 15, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Asthma; Allergy; Psychiatry; Growth; Cognition; Childhood; Development; Infections; Eczema; Bone development
• Additional Relevant MeSH Terms: Wounds and Injuries; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Skin Diseases; Otorhinolaryngologic Diseases; Signs and Symptoms, Respiratory; Skin Diseases, Eczematous; Laryngeal Diseases; Dermatitis; Laryngitis; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Asthma; Hypersensitivity; Fractures, Bone; Mental Disorders; Infections; Eczema; Respiratory Tract Infections; Respiratory Sounds; Croup; Fatty Acids; Lipids; Fatty Acids, Unsaturated; Oils; Dietary Fats; Fats; Dietary Fats, Unsaturated; Fish Oils; Fatty Acids, Omega-3
• Other Study ID Numbers: H-23055833-F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No